tbuckley/cabot-search huggingface dataset:
Can the Artificial Intelligence System for Urine Microalbuminuria Detection Monitor the Progression of Diabetic Kidney Disease in the Clinical Laboratory?
Authors: Xiaozhe Lin, Yingxiu Xiao, Yaqiong Tian, Bizhen Cheng, Xiaoyang Jiao, Xinran Yang, Yongni Wang, Wenjing Xiong, Wenyan Guo, Qingyu Wu, Qiaoxin Zhang
Journal: Diabetes Care (2022)

The artificial intelligence (AI) system containing autoverification and autoguidance subsystems for urine microalbuminuria (Uma) detection is established in this study to not only enhance laboratory physician efficiency but also monitor the progression of diabetes kidney disease (DKD).The Uma detection includes Uma, urine creatinine and urine albumin-creatinine ratio (ACR) items.After verification of the detection results through the autoverification subsystem, a series of recommendations on diagnosis or further disposal of DKD to the clinician is put forward by the autoguidance subsystem.A total of 351 clinical cases was used to establish the autoverification subsystem for Uma, which included the rules of the switch, instrument alarm, samples, quality control, detection limits, and consistency check according to the AUTO10-A document issued by the American Clinical Laboratory Standards Institute (1).Meanwhile, nine recommendations for the autoguidance subsystem were established according to the diagnostic guides of DKD (2,3) and diabetes (4).Recommendations will be provided with one or more of the following: R1) Possible DKD, please combine with fundus examination.R2)
Adjusted Cutoff Scores Increase Sensitivity of Depression Screening Measures in Adolescents With Type 1 Diabetes
Authors: Arwen M. Marker, Susana R. Patton, Mark A. Clements, Anna E. Egan, Ryan J. McDonough
Journal: Diabetes Care (2022)

OBJECTIVE To measure the acceptability and diagnostic accuracy of commonly used depression screening measures to determine ideal cutoff scores that sensitively identify depressive disorders in adolescents with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS One hundred adolescents (12–17 years old) completed a reference standard, semistructured diagnostic interview and both long and short versions of five commonly used depression screening measures in the United States. To assess feasibility and acceptability, we used screener completion time and participant ratings, respectively. We used descriptive statistics, area under the receiver operating characteristic (ROC) curve analyses, and paired-sample area differences under the ROC curve to assess each measure’s diagnostic validity against our reference standard and to determine ideal cutoff scores for this sample. RESULTS Adolescents had a mean age of 15.0 ± 1.7 years, time since T1D diagnosis of 6.0 ± 4.1 years, and glycated hemoglobin (HbA1c) of 8.9 ± 1.8%. Sixty percent of adolescents were male, 15% endorsed a current depressive disorder, and 15% endorsed lifetime suicidality. Measures demonstrated low sensitivity (0.33–0.67) to detect current depressive disorders using preexisting cutoff scores. However, adjusted cutoff scores increased sensitivity and reduced false negatives. All depression screening measures demonstrated “good” to “excellent” predictive validity, and the Children’s Depression Inventory-2 Short version demonstrated significantly greater diagnostic accuracy than the Patient Health Questionnare-2 item version for adolescents. CONCLUSIONS Clinics should consider using screening measures with the greatest diagnostic accuracy as identified in this study and adjusting measure cutoff scores to increase sensitivity and reduce false negatives.
Initiation of New Glucose-Lowering Therapies May Act to Reduce Physical Activity Levels: Pooled Analysis From Three Randomized Trials
Authors: Thomas Yates, Jack A. Sargeant, James A. King, Joe Henson, Charlotte L. Edwardson, Emma Redman, Gaurav S. Gulsin, Emer M. Brady, Ehtasham Ahmad, David J. Stensel, David R. Webb, Gerry P. McCann, Kamlesh Khunti, Melanie J. Davies
Journal: Diabetes Care (2022)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce body weight and improve cardiometabolic health, but their effect on physical activity is unknown.We pooled data (n = 148) from three randomized trials to investigate the effect of empagliflozin (SGLT2i) and liraglutide (GLP-1RA), in comparison with sitagliptin (dipeptidyl peptidase 4 inhibitor) and dietary therapies, on accelerometer-assessed physical activity.Liraglutide (mean -1,144 steps/day; 95% CI -2,069 to -220), empagliflozin (-1,132 steps/day; -1,739, -524), and sitagliptin (-852 steps/day; -1,625, -78) resulted in reduced total daily physical activity after 6 months (P < 0.01 vs. control). Moderate- to vigorous-intensity physical activity was also reduced. Dietary interventions led to no change or an increase in physical activity.The initiation of all glucose-lowering therapies was associated with reduced physical activity, warranting further investigation.
The Primary Immunodeficiencies
Authors: Fred S. Rosen, Max D. Cooper, Ralph J.P. Wedgwood
Journal: New England Journal of Medicine (1995)

The primary immunodeficiency disorders reflect abnormalities in the development and maturation of cells of the immune system. These defects result in an increased susceptibility to infection; recurrent pyogenic infections occur with defects of humoral immunity, and opportunistic infections with defects of cell-mediated immunity. These two broad categories of illness correspond roughly to defects in the two principal types of immunocompetent cells, B lymphocytes and T lymphocytes. Defective development of B cells results in abnormalities in humoral immunity, whereas defects in the development of T cells cause problems with cellular immunity.When pathogens are taken up by macrophages or dendritic cells, . . .
KEAP1‐NRF2 protein–protein interaction inhibitors: Design, pharmacological properties and therapeutic potential
Authors: Enrique Crisman, Pablo Duarte, Esteban Dauden, Antonio Cuadrado, María Isabel Rodríguez‐Franco, Manuela G. López, Rafael León
Journal: Medicinal Research Reviews (2022)

Abstract The transcription factor nuclear factor erythroid 2‐related factor 2 (NRF2) is considered the master regulator of the phase II antioxidant response. It controls a plethora of cytoprotective genes related to oxidative stress, inflammation, and protein homeostasis, among other processes. Activation of these pathways has been described in numerous pathologies including cancer, cardiovascular, respiratory, renal, digestive, metabolic, autoimmune, and neurodegenerative diseases. Considering the increasing interest of discovering novel NRF2 activators due to its clinical application, initial efforts were devoted to the development of electrophilic drugs able to induce NRF2 nuclear accumulation by targeting its natural repressor protein Kelch‐like ECH‐associated protein 1 (KEAP1) through covalent modifications on cysteine residues. However, off‐target effects of these drugs prompted the development of an innovative strategy, the search of KEAP1‐NRF2 protein–protein interaction (PPI) inhibitors. These innovative activators are proposed to target NRF2 in a more selective way, leading to potentially improved drugs with the application for a variety of diseases that are currently under investigation. In this review, we summarize known KEAP1‐NRF2 PPI inhibitors to date and the bases of their design highlighting the most important features of their respective interactions. We also discuss the preclinical pharmacological properties described for the most promising compounds.
Breakthrough SARS‐CoV‐2 infection outcomes in vaccinated patients with chronic liver disease and cirrhosis: A National COVID Cohort Collaborative study
Authors: Jin Ge, Jean C. Digitale, Mark J. Pletcher, Jennifer C. Lai
Journal: Hepatology (2022)

Background and Aims: Outcomes of breakthrough SARS‐CoV‐2 infections have not been well characterized in non‐veteran vaccinated patients with chronic liver diseases (CLD). We used the National COVID Cohort Collaborative (N3C) to describe these outcomes. Approach and Results: We identified all CLD patients with or without cirrhosis who had SARS‐CoV‐2 testing in the N3C Data Enclave as of January 15, 2022. We used Poisson regression to estimate incidence rates of breakthrough infections and Cox survival analyses to associate vaccination status with all‐cause mortality at 30 days among infected CLD patients. We isolated 278,457 total CLD patients: 43,079 (15%) vaccinated and 235,378 (85%) unvaccinated. Of 43,079 vaccinated patients, 32,838 (76%) were without cirrhosis and 10,441 (24%) with cirrhosis. Breakthrough infection incidences were 5.4 and 4.9 per 1000 person‐months for fully vaccinated CLD patients without cirrhosis and with cirrhosis, respectively. Of the 68,048 unvaccinated and 10,441 vaccinated CLD patients with cirrhosis, 15% and 3.7%, respectively, developed SARS‐CoV‐2 infection. The 30‐day outcome of mechanical ventilation or death after SARS‐CoV‐2 infection for unvaccinated and vaccinated CLD patients with cirrhosis were 15.2% and 7.7%, respectively. Compared to unvaccinated patients with cirrhosis, full vaccination was associated with a 0.34‐times adjusted hazard of death at 30 days. Conclusions: In this N3C study, breakthrough infection rates were similar among CLD patients with and without cirrhosis. Full vaccination was associated with a 66% reduction in risk of all‐cause mortality for breakthrough infection among CLD patients with cirrhosis. These results provide an additional impetus for increasing vaccination uptake in CLD populations.
Delayed Hemolytic Transfusion Reactions
Authors: Dilip Solanki
Journal: JAMA (1978)

Delayed hemolytic transfusion reactions in eight persons were manifested solely or primarily by an apparently unexplained posttransfusion decrease in the hematocrit value. Alloantibodies were eventually found in all eight patients, but were sometimes undetectable for as long as 72 hours after the reaction. This did not preclude the occurrence of a new, acute hemolytic reaction. There were three instances of reversible renal failure complicating the reaction. In two patients, some or all of the antibodies became undetectable after four and nine months. In a third, the indirect antiglobulin reactions became considerably weaker after 12 months. Patients previously sensitized to RBC antigens should have available records inspected and a warning device (wristband or wallet card) provided to help prevent reactions caused by an anamnestic antibody rise. (<i>JAMA</i>239:729-731, 1978)
Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN
Authors: Eileen Morgan, Melina Arnold, A Gini, V Lorenzoni, C J Cabasag, Mathieu Laversanne, Jerome Vignat, Jacques Ferlay, Neil Murphy, Freddie Bray
Journal: Gut (2022)

Objective Colorectal cancer (CRC) is the third most common cancer worldwide. The geographical and temporal burden of this cancer provides insights into risk factor prevalence and progress in cancer control strategies. We examine the current and future burden of CRC in 185 countries in 2020 and 2040. Methods Data on CRC cases and deaths were extracted from the GLOBOCAN database for the year 2020. Age-standardised incidence and mortality rates were calculated by sex, country, world region and Human Development Index (HDI) for 185 countries. Age-specific rates were also estimated. The predicted number of cases and deaths in 2040 were calculated based on global demographic projections by HDI. Results Over 1.9 million new CRC cases and 930 000 deaths were estimated in 2020. Incidence rates were highest in Australia/ New Zealand and European regions (40.6 per 100 000, males) and lowest in several African regions and Southern Asia (4.4 per 100 000, females). Similar patterns were observed for mortality rates, with the highest observed in Eastern Europe (20.2 per 100 000, males) and the lowest in Southern Asia (2.5 per 100 000, females). The burden of CRC is projected to increase to 3.2 million new cases and 1.6 million deaths by 2040 with most cases predicted to occur in high or very high HDI countries. Conclusions CRC is a highly frequent cancer worldwide, and largely preventable through changes in modifiable risk factors, alongside the detection and removal of precancerous lesions. With increasing rates in transitioning countries and younger adults, there is a pressing need to better understand and act on findings to avert future cases and deaths from the disease.
MCPIP1 restrains mucosal inflammation by orchestrating the intestinal monocyte to macrophage maturation via an ATF3-AP1S2 axis
Authors: Huiying Lu, Cui Zhang, Wei Wu, Huimin Chen, Ritian Lin, Ruicong Sun, Xiang Gao, Gengfeng Li, Qiong He, Han Gao, Xiaohan Wu, Jian Lin, Ruixin Zhu, Jianli Niu, Pappachan E Kolattukudy, Zhanju Liu
Journal: Gut (2022)

Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) is highly expressed in inflamed mucosa of inflammatory bowel disease (IBD) and negatively regulates immune response, while the underlying mechanisms regulating mucosal macrophage functions remain unknown. Here, we investigated the roles of MCPIP1 in modulating the differentiation and functions of intestinal macrophages in the pathogenesis of IBD.ScRNA-seq was used to cluster the monocyte/macrophage lineage from macrophage-specific Mcpip1-deficient (Mcpip1∆Mye) mice and Mcpip1fl/fl littermates. The differentially expressed genes were confirmed by RNA-seq, luciferase assay, CUT&Tag assay and Western blotting. Effects of MCPIP1 and the activating transcription factor 3 (ATF3)-AP1S2 axis were assessed in patients with IBD.Mcpip1∆Mye mice developed more severe dextran sulfate sodium (DSS)-induced colitis characterised by an increase in macrophage migratory capacity and M1 macrophage polarisation but a decrease in the monocyte-to-macrophage maturation in gut mucosa compared with their littermates. ScRNA-seq unravelled a proinflammatory population (Ccr2+Il-1β+Tlr2+Cx3cr1-Cd163-Mrc1-Ly6c+) of the monocyte/macrophage lineage from lamina propria CD11b+ cells and an arrest of Mcpip1∆Mye monocyte-to-macrophage maturation in an Atf3-Ap1s2 axis-dependent manner. Silencing of Ap1s2 or Atf3 markedly suppressed Mcpip1∆Mye macrophage migration, M1-like polarisation, and production of proinflammatory cytokines and chemokines. Notably, in vivo blockage of Ap1s2 ameliorated DSS-induced colitis in Mcpip1ΔMye mice through enhancing intestinal macrophage maturation. Furthermore, MCPIP1, ATF3 and AP1S2 were highly expressed in inflamed mucosa of active patients with IBD and blockage of ATF3 or AP1S2 significantly suppressed IBD CD14+-derived M1-like macrophage polarisation and proinflammatory cytokine production.Macrophage-specific Mcpip1 deficiency polarises macrophages towards M1-like phenotype, arrests macrophage maturation and exacerbates intestinal inflammation in an Atf3-Ap1s2-dependent manner, thus providing novel mechanistic insight into intestinal macrophage functions during IBD.
OA09.03 Single Cell Analyses Reveal Effects of Immunosenescence Cells in Neoadjuvant Immunotherapy of Lung Squamous cell Carcinoma Patients
Authors: C. Yan, Z. Hui, Q. Wang, S. Xiao, Y. Pu, Q. Wang, T. Wang, J. You, X. Ren
Journal: Journal of Thoracic Oncology (2022)
OA10.05 Integrating Smoking Cessation into LDCT Lung Cancer Screening. Results of the Ontario, Canada, Pilot
Authors: B.K. Evans, M. Tammemagi, M. Walker, E. Cameron, Y. Leung, C. Bravo, C. McGarry, M. Rey, R. Truscott, G. Darling, L. Rabeneck
Journal: Journal of Thoracic Oncology (2022)
MA01.09 Characterising Aggressive Pulmonary Carcinoids Through Integrative Omics Analysis Within the lungNENomics Project
Authors: A. Sexton-Oates, A. Di Genova, L. Mangiante, C. Voegele, S. Tabone-Eglinger, T. Walter, A. Ghantous, C. Cuenin, P. Nürnberg, J. Altmüller, A. Boland, J.-F. Deleuze, N. lungNEN network, E.-J. Speel, A.-M. Dingemans, L. Moonen, J. Derks, T. Dayton, F. Damiola, N. Girard, S. Lantuejoul, N. Alcala, M. Foll, L. Fernandez-Cuesta
Journal: Journal of Thoracic Oncology (2022)
National Estimates of Nonfatal Firearm-Related Injuries
Authors: Joseph L. Annest
Journal: JAMA (1995)

<h3>Objective.</h3> —To describe the magnitude and characteristics of nonfatal firearm-related injuries treated in hospital emergency departments in the United States and to compare nonfatal injury rates with firearm-related fatality rates. <h3>Design.</h3> —Data were obtained from medical records for all firearm-related injury cases identified using the National Electronic Injury Surveillance System (NEISS) from June 1, 1992, through May 31, 1993. <h3>Setting.</h3> —NEISS comprises 91 hospitals that are a stratified probability sample of all hospitals in the United States and its territories that have at least six beds and provide 24-hour emergency service. <h3>Main Outcome Measures.</h3> —Numbers and population rates for nonfatal and fatal firearm-related injuries. <h3>Results.</h3> —An estimated 99 025 (95% confidence interval [CI], 56 325 to 141 725) persons (or 38.6 per 100000 population; 95% CI, 22.0 to 55.2) were treated for nonfatal firearm-related injuries in US hospital emergency departments during the study period. The rate of nonfatal firearm-related injuries treated was 2.6 (95% CI, 1.5 to 3.7) times the national rate of fatal firearm-related injuries for 1992. <h3>Conclusions.</h3> —Nonfatal firearm-related injuries contribute substantially to the overall public health burden of firearm-related injuries. NEISS can be useful to monitor the number of nonfatal firearm-related injuries in the United States. A national surveillance system is needed to provide uniform data on firearm-related injury morbidity and mortality for use in research and prevention efforts. (<i>JAMA</i>. 1995;273:1749-1754)
Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma Via STING signaling
Authors: Zongjuan Li, Yang Zhang, Weifeng Hong, Biao Wang, Yixing Chen, Ping Yang, Jian Zhou, Jia Fan, Zhaochong Zeng, Shisuo Du
Journal: Gut Microbes (2022)

Studies of the gut–liver axis have enhanced our understanding of the pathophysiology of various liver diseases and the mechanisms underlying the regulation of the effectiveness of therapies. Radiotherapy (RT) is an important therapeutic option for patients with unresectable hepatocellular carcinoma (HCC). However, the role of the microbiome in regulating the response to RT remains unclear. The present study characterizes the gut microbiome of patients responsive or non-responsive to RT and investigates the molecular mechanisms underlying the differences in patient response. We collected fecal samples for 16S rRNA sequencing from a prospective longitudinal trial of 24 HCC patients receiving RT. We used fecal microbiota transplantation (FMT), flow cytometry, and transcriptome sequencing to explore the effects of dysbiosis on RT. We also examined the role of stimulator of interferon genes (STING) in RT-associated antitumor immune responses mediated by gut microbiota in STING- (Tmem173−/−) and cGAS-knockout (Mb21d1–/–) mouse models. We propose that primary resistance to RT could be attributed to the disruption of the gut microbiome. Mechanistically, gut microbiome dysbiosis impairs antitumor immune responses by suppressing antigen presentation and inhibiting effector T cell functions through the cGAS–STING–IFN-I pathway. Cyclic-di-AMP – an emerging second messenger of bacteria – may act as a STING agonist and is thus a potential target for the prediction and modulation of responses to RT in HCC patients. Our study highlights the therapeutic potential of modulating the gut microbiome in HCC patients receiving RT and provides a new strategy for the radiosensitization of liver cancer.
Heart failure outcomes according to heart rate and effects of empagliflozin in patients of the EMPEROR‐Preserved trial
Authors: Michael Böhm, Javed Butler, Felix Mahfoud, Gerasimos Filippatos, João Pedro Ferreira, Stuart J. Pocock, Jonathan Slawik, Martina Brueckmann, Bruno Linetzky, Elke Schüler, Christoph Wanner, Faiez Zannad, Milton Packer, Stefan D. Anker
Journal: European Journal of Heart Failure (2022)

Aims Empagliflozin reduces cardiovascular death (CVD) or heart failure hospitalization (HHF) in patients with heart failure and preserved ejection fraction (HFpEF). Treatment effects and safety in relation to resting heart rate (RHR) have not been studied. Methods and results The interplay of RHR and empagliflozin effects in EMPEROR‐Preserved was evaluated. We grouped patients ( n = 5988) according to their baseline RHR (&lt;70 bpm [ n = 2650], 70–75 bpm [ n = 967], &gt;75 bpm [ n = 1736]) and explored the influence of RHR on CVD or HHF (primary outcome) and its components in sinus rhythm or atrial fibrillation/flutter (AF) and adverse events. We studied the efficacy of empagliflozin across the RHR spectrum. Compared to placebo, empagliflozin did not change heart rate over time. The primary outcome ( p for trend = 0.0004) and its components CVD ( p trend = 0.0002), first HHF ( p for trend = 0.0099) and all‐cause death ( p &lt; 0.0001) increased with RHR only in sinus rhythm but not AF. The risk increase with RHR was similar in patients with heart failure and mildly reduced ejection fraction (left ventricular ejection fraction [LVEF] 40–49%) and HFpEF (LVEF ≥50%). Baseline RHR had no influence on the effect of empagliflozin on the primary outcomes ( p for trend = 0.20), first HHF ( p for trend = 0.49). There were no clinically relevant differences in adverse events between empagliflozin and placebo across the RHR groups. Conclusion Resting heart rate associates with outcomes only in sinus rhythm but not in AF. Empagliflozin reduced outcomes over the entire RHR spectrum without increase of adverse events.
Targeting cancer cachexia: Molecular mechanisms and clinical study
Authors: Yong‐Fei Wang, Zi‐Yi An, Dong‐Hai Lin, Wei‐Lin Jin
Journal: MedComm (2022)

Cancer cachexia is a complex systemic catabolism syndrome characterized by muscle wasting. It affects multiple distant organs and their crosstalk with cancer constitute cancer cachexia environment. During the occurrence and progression of cancer cachexia, interactions of aberrant organs with cancer cells or other organs in a cancer cachexia environment initiate a cascade of stress reactions and destroy multiple organs including the liver, heart, pancreas, intestine, brain, bone, and spleen in metabolism, neural, and immune homeostasis. The role of involved organs turned from inhibiting tumor growth into promoting cancer cachexia in cancer progression. In this review, we depicted the complicated relationship of cancer cachexia with the metabolism, neural, and immune homeostasis imbalance in multiple organs in a cancer cachexia environment and summarized the treatment progress in recent years. And we discussed the molecular mechanism and clinical study of cancer cachexia from the perspective of multiple organs metabolic, neurological, and immunological abnormalities. Updated understanding of cancer cachexia might facilitate the exploration of biomarkers and novel therapeutic targets of cancer cachexia.